HIF-1α is necessary to support gluconeogenesis during liver regeneration

Toshihide Tajima, Nobuhito Goda, Natsuko Fujiki, Takako Hishiki, Yasumasa Nishiyama, Nanami Senoo-Matsuda, Motohide Shimazu, Tomoyoshi Soga, Yasunori Yoshimura, Randall S. Johnson, Makoto Suematsu

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43 Citations (Scopus)

Abstract

Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1α (HIF-1α) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72 h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1α in the regulation of gluconeogenesis under liver regeneration.

Original languageEnglish
Pages (from-to)789-794
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume387
Issue number4
DOIs
Publication statusPublished - 2009 Oct 2

Keywords

  • Gluconeogenesis
  • Hypoxia inducible factor-1
  • Liver regeneration
  • Metabolome
  • Phosphoenolpyruvate carboxykinase
  • Phosphoglycerate kinase 1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Tajima, T., Goda, N., Fujiki, N., Hishiki, T., Nishiyama, Y., Senoo-Matsuda, N., Shimazu, M., Soga, T., Yoshimura, Y., Johnson, R. S., & Suematsu, M. (2009). HIF-1α is necessary to support gluconeogenesis during liver regeneration. Biochemical and Biophysical Research Communications, 387(4), 789-794. https://doi.org/10.1016/j.bbrc.2009.07.115